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Stimulants (MPH, AMP) for ADHD


Stimulants (MPH, AMP) for ADHD

Stimulants (psychotonics, psychoanaleptics, stimulants, colloquially: upper; singular: Stimulants) are psychotropic substances that have a stimulating effect by increasing, accelerating or improving nerve activity.
The opposite are tranquilizers (sedatives, colloquially: downers).

ADHD medications are divided into stimulants (methylphenidate, amphetamine medications) and non-stimulants (atomoxetine, guanfacine and others).

1. Stimulants from a chemical perspective

  • Phenethylamines
    Phenethylamine is the chemical parent substance of all naturally and artificially produced phenethylamines. It is the parent chemical group and is a so-called trace amine, as it is only found in small quantities in the body. Many substances within this large group have a psychotropic effect.
    • Catecholamines
      • Dopamine
      • Noradrenaline
      • Adrenalin
    • Phenylethylamine
      • Methylphenidate
    • Amphetamines
      A group of mostly artificially produced phenethylamines, which are also known as wake-up amines due to their stimulating effect
      • Dexamphetamine
        • Active ingredient in many ADHD amphetamine medications
      • Methamphetamine
        • was developed at the end of the 19th century and used as a war drug (Pervitin, on the market in Germany until 1988; Desoxyn (USA))
        • common in the drug scene as “meth”, “crystal” or “crystal meth”, among others
      • Cathinone.
        These are both natural and artificial amphetamines, which differ only slightly chemically from the main substance amphetamine (amphetamine derivatives).
        • Bupropion

(Thanks to Nephilim)

2. Stimulants as medication versus stimulants as a drug

Amphetamines are also traded and consumed illegally as drugs (e.g. as ecstasy, crystal meth).
As with any drug, the amount and method of use determine whether it is helpful or harmful. With amphetamines, the intoxicating effect is caused by

  • Massively higher dosage than as a drug
    • Only a high dosage occupies more than 50 % of the dopamine receptors and thus enough to cause a perception of intoxication1
    • Only the high dosage leads to the release of dopamine via the VMAT2 receptors.
      AMP drugs, which have a purely reuptake-inhibiting effect, do not use this route of action
  • Rapid absorption of active ingredients (e.g. through the nose)1
    • Even a high dosage, which is taken slowly, does not act like a drug
  • Short duration of action (a high speed of change in the dopamine level upwards and downwards is crucial)1

Stimulants are low-dose drugs that have a long-term, consistent effect and are also administered orally, which means that the active ingredients are distributed so slowly that no intoxicating effect can occur.
When taken as prescribed by a doctor, there are no known addictive effects, which unfortunately cannot be said of many other medically prescribed drugs.

Unretarded MPH, taken in succession, like retarded MPH, sets several dopamine maxima (all of which are so low that they do not develop a drug effect). Lisdexamfetamine, on the other hand, sets only one maximum and thus causes a more even inhibition of dopamine (and noradrenaline) reuptake.
In order to increase DA and NE levels as evenly as possible with unretarded MPH, it should be administered at shorter intervals (2 to 2.5 hours) than the optimal single dose. So instead of administering 7.5 mg every 3.5 hours (for example), an administration of 5 mg every 2.5 hours would result in more even DA and NE levels and thus better symptom reduction. Stahl illustrates the difference between short-term high/rapidly decreasing stimulant levels (= phasic DA) and low long-term constant stimulant levels (= tonic DA) as the decisive difference between drug effect and curative drug effect.2

3. Stimulants as ADHD medication reduce the risk of addiction

3.1. ADHD medication reduces the risk of developing addiction

Stimulants also do not increase the risk of developing an addiction to non-medical stimulants.3 On the contrary, stimulants as ADHD medications significantly and sustainably reduce the risk of addiction. A case report provides an example.4

Another study reports that factors such as the start and discontinuation of medication use for ADHD could have an influence on the likelihood of later addiction.5 However, it should be noted that addiction is epidemic in the USA (one in 13 Americans has a diagnosis of addiction), which can be attributed in particular to inappropriate painkiller prescriptions (opioids), which never occurred in Europe. The extent to which the study could be transferred to conditions outside the USA and especially in Europe is unclear.

A meta-analysis of 6 studies with n = 1,014 subjects showed a significantly reduced risk of later addiction for participants medicated with stimulants (here: MPH).6 The risk of later addiction, whether to alcohol or other substances, was found to be 1.9 times lower (i.e. almost halved).7

Amphetamine drugs are now available as pro-drugs (lisdexamfetamine). This means that they are available in a form in which they are simply ineffective when abused (abusive ingestion in massive overdoses through the nose or intravenously) because they are present in an active substance compound, are only metabolized over many hours in the blood, very slowly, to the active drug substance and therefore cannot trigger a drug high, but can only bring about the healing effect of a flatly rising and falling functional dopamine level.
Daberkow et al8 show in this Graph under D the slow increase in dopamine (drug) at 1 mg/kg AMP and the rapid increase (drug) at 10 mg/kg AMP. The level development at 1 mg/kg AMP corresponds to the curves known from amphetamine drugs.

3.2. ADHD medication reduces addictive behavior with existing addiction

ADHD sufferers with comorbid cocaine addiction showed a significant reduction in addictive behavior when treated with stimulants, corresponding to the reduction in ADHD symptoms.9

Nevertheless, ADHD sufferers with a pre-existing acute or previous addiction (dependence) to amphetamines or cocaine should take into account that the receipt of similarly acting drugs could trigger them to try to abuse them again as a drug.
Other acute or former addictions (alcohol, THC without amphetamine addiction) are unlikely to have a trigger effect.
Isolated amphetamine abuse (weekend use) is also unlikely to pose a risk and, even if repeated, is more likely to be a sign of self-medication.
It should also be borne in mind that there are cheaper and easier to obtain substances in every disco and behind every train station that produce considerably more intoxicating effects.

  1. Stahl (2013): Stahl’s Essential Psychopharmacology. Neuroscientific Basis and Practical Applications. 4th Edition. Seite 310

  2. Stahl (2013): Stahl’s Essential Psychopharmacology, 4. Auflage, Chapter 12: Attention deficit hyperactivity disorder and its treatment, Seite 495

  3. McCabe VV, Veliz PT, Wilens TE, Schepis TS, Pasman E, Evans-Polce RJ, McCabe SE (2024): Adolescents’ Use of Medications for Attention-Deficit/Hyperactivity Disorder and Subsequent Risk of Nonmedical Stimulant Use. J Adolesc Health. 2024 Mar 13:S1054-139X(24)00060-0. doi: 10.1016/j.jadohealth.2024.01.024. PMID: 38483378. n = 11.905

  4. Levine J, Swanson H (2023): The Use of Lisdexamfetamine to Treat ADHD in a Patient with Stimulant (Methamphetamine) Use Disorder. Case Rep Psychiatry. 2023 Aug 14;2023:5574677. doi: 10.1155/2023/5574677. PMID: 37609571; PMCID: PMC10442178.

  5. Fouladvand, Hankosky, Bush, Chen, Dwoskin, Freeman, Henderson, Kantak, Talbert, Tao, Zhang (2019): Predicting substance use disorder using long-term attention deficit hyperactivity disorder medication records in Truven. Health Informatics J. 2019 May 19:1460458219844075. doi: 10.1177/1460458219844075.

  6. Wilens, Faraone, Biederman, Gunawardene (2003): Does stimulant therapy of attention-deficit/hyperactivity disorder beget later substance abuse? A meta-analytic review of the literature; Pediatrics. 2003 Jan;111(1):179-85.

  7. Edel, Vollmoeller (2006): Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung bei Erwachsenen, Springer, Seite 120

  8. Daberkow DP, Brown HD, Bunner KD, Kraniotis SA, Doellman MA, Ragozzino ME, Garris PA, Roitman MF (2013): Amphetamine paradoxically augments exocytotic dopamine release and phasic dopamine signals. J Neurosci. 2013 Jan 9;33(2):452-63. doi: 10.1523/JNEUROSCI.2136-12.2013. PMID: 23303926; PMCID: PMC3711765.

  9. Manni, Cipollone, Pallucchini, Maremmani, Perugi, Maremmani (2019): Remarkable Reduction of Cocaine Use in Dual Disorder (Adult Attention Deficit Hyperactive Disorder/Cocaine Use Disorder) Patients Treated with Medications for ADHD. Int J Environ Res Public Health. 2019 Oct 15;16(20). pii: E3911. doi: 10.3390/ijerph16203911.

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